The purpose of U.S. Pharmacopeia (USP) 797 is to provide the practice standards to help ensure that compounded sterile preparations are of high quality, and is for the pre-administration phase of sterile preparations. It describes the CSP requirements (guidelines, USP 797 procedures and compliance) for CSPs and sets the standards that apply to all settings in which sterile preparations are compounded. Adherence to 797 will reduce the potential for contamination caused by unclean environment, pharmacist error, lack of quality control, incorrect beyond-use dating and other factors. The standard applies to anyone who prepares CSPs and all places where they are prepared. CSPs include drugs, nutrients, biologics, diagnostics and radiopharmaceuticals. The guideline requires environmental controls to include a separate area for compounding that meets a definite level of cleanliness, and monitoring to guarantee that control is maintained.

Important to all preparers and places where CSPs are prepared is that the Joint Commission requires a gap analysis and action plan for USP 797 compliance, and is enforcing USP Chapter 797 within their standards. They may require stricter compliance to 797 than the states’ Board of Pharmacy.

States Board of Pharmacy Positions

The PA State Board posts a Special Notice on their web site which, in part, states that “the provisions of the USP are not part of the Pharmacy Act’s substantive sections or Board regulations.” It further states, “The Board is not authorized to provide advisory opinions or interpretations except through promulgating regulations and adjudicating disciplinary actions, therefore the Board cannot offer any guidance to pharmacists on how to proceed with the new standards set by USP 797 and takes no position on USP 797.” However, in the second half of their statement they caution, “Section 5(a)(12) of the Pharmacy Act provides that the departure from, or failure to conform to, the standards of acceptable and prevailing pharmacy practice is grossly unprofessional conduct. While the Board cannot definitely say that pharmacists will face disciplinary action for the failure to follow USP 797, the possibility does exist.”

USP 797 has been accepted and adopted by several states. It is under review by numerous others. States have the choice to implement 797 exactly or to edit the standards into pharmacy regulations. New Jersey, for example, requires that the buffer zone be an ISO 6 / Class 1,000 clean room.

USP 797 assigns each CSP one of five potential contamination risk levels: immediate use, low, low with 12 hours or less beyond use date (BUD), medium, high. The risk level depends on the CSPs compounding environment; its potential for microbial, chemical, and physical contamination; the nature of production of the CSP. It is the responsibility of personnel to determine the correct level.

Barring exemptions for immediate-use (<3) CSPs for non-hazardous sterile drugs only, which must have administration begun within 1 hr. after start of preparation, the levels break down as follows:

High-Risk Level occurs when CSPs are prepared from non-sterile ingredients, or from sterile ingredients but the environment is below ISO Class 5. It also occurs if more than six hours passes between compounding and sterilization and/or the purity of compounds are not verified by documentation.

Medium-Risk Level occurs in an ISO Class 5 environment and involves complex procedures, like bulk compounding, which could occur over an extended period. It also includes using pooled sterile commercial products for multiple patients or for one patient multiple times, as in Chemotherapy or pain management administered by an infusion device

Low-risk level compounding occurs in an ISO Class 5 environment and involves only a few basic, steps. It could apply in reconstituting single-dose vials of antibiotics, simple transfers of sterile products or preparing hydration solutions. There is also a subsection of low risk designed for facilities with no ISO 7 secondary control clean room the low-risk level with 12 hour or less Beyond Use Date (BUD). This category is for those products that are low risk and will be administered within 12 hours of compounding.

Single-Dose vs. Multiple Dose Containers

Single dose vials (SDV), if opened or punctured in a better than ISO 5 area, may be used for up to 6 hours. Opened or needle-punctured single-dose containers must be used within one hour if opened in worse than ISO Class 5 air quality and remaining contents discarded. Opened single-dose ampuls must be discarded and may not be stored for any time period. The BUD for opened or entered multiple-dose containers is 28 days, unless otherwise specified by the manufacturer. Additionally, in Multiple-dose and single-dose sterile products or CSPs for use as multiple-dose applications, combining is forbidden.

Hazardous Drugs as CSPs

The section on hazardous drugs is aimed at protecting handlers from exposure to certain drugs during preparation. It has been revised so that the agents are the same as those listed in the NIOSH guidelines (http://www.cdc.gov/NIOSH/), and references the NIOSH Alert regarding choosing the appropriate Primary Engineering Control (PEC). It recommends PECs that do not recirculate air

When compounding hazardous drugs, a biological safety cabinet (BSC) or compounding aseptic containment isolator (CACI) must be used. All hazardous drugs must be stored and prepared in a negative pressure ISO 7 with an ISO 7 ante area. BSCs or CACIs should be vented to the outside. Of course, waste disposal should be according to state and federal regulations.

Radiopharmaceuticals as CSPs

Highly particulate generating materials, like lead containers, are required to be used for the protection of handlers. ISO Class 8 air is permitted because it is hard to maintain air cleanliness with all of the lead shielding being used.

Therefore, when preparing these CSPs the guidelines are:

Must be prepared in an ISO 5 containment device in an ISO 8 environment or cleaner

Principals of ALARA followed (as low as reasonably achievable)

Allowance for preparation of radiopharmaceuticals under the Low-Risk Level with 12 hr BUD – hot labs in hospitals have better chance of compliance as long as they have ISO Class 5 PEC

Allergen Extracts as CSPs

Unpreserved allergen extracts must fully comply with 797, but most allergen extracts are highly preserved. Preparations using preserved allergen extracts are exempt from certain aspects of USP 797 under certain conditions involving:

Hand hygiene

PPE used

Simple aseptic transfer

Contain effective amount of preservative

Single patient only

Gloves are disinfected with IPA

Vial stoppers disinfected

Labeling requirements

Environmental Quality and Control

The related revisions deal with environmental designs and primary engineering control areas, including CAIs (barrier isolators), HEPA filters, buffer and anterooms, and cleanrooms. They clarify ISO cleanliness requirements and placement of equipment in compounding facilities.

Laminar air flow workbenches (LAFW), BSC, CAI, and CACI contributions can count toward the total number of air changes per hour to meet ISO Class 7 requirements.

USP 797 Related Organizations:USP797.org is a privately-owned resource developed to aid public understanding of the USP 797 regulation developed by U.S. Pharmacopoeia, and its JCAHO-mandated schedule for implementation.

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Tom has over 36 years of environmental engineering and health and safety experience in project management, process safety management, air quality compliance, strategic planning, and environmental control systems design. His services have included work in 22 states for the chemical, pharmaceutical, printing and surface coating, electronics, food, metals, healthcare, and other industries.

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